Selenium-Catalyzed Oxidative C-H Amination of (E)-3-(Arylamino)-2-styrylquinazolin-4(3 H)-ones: A Metal-Free Synthesis of 1,2-Diarylpyrazolo[5,1- b]quinazolin-9(1 H)-ones

Article abstract of DOI:10.1021/acs.joc.8b03179

A novel metal-free catalysis protocol for the synthesis of 1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-ones via intramolecular oxidative C-H amination of (E)-3-(arylamino)-2-styrylquinazolin-4(3H)-ones has been developed in moderate to good yield. The metho

Full text of DOI:10.1021/acs.joc.8b03179

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Article
Selenium-catalyzed oxidative C-H amination of (E)-3-
(arylamino)-2-styrylquinazolin-4(3H)-ones: a metal-free
synthesis of 1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-ones
Yetong Zhang, Yinlin Shao, Julin Gong, Jianghe Zhu, Tianxing Cheng, and Jiuxi Chen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03179 • Publication Date (Web): 11 Feb 2019
Downloaded from http://pubs.acs.org on February 11, 2019
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Selenium-catalyzed
(E)-3-(arylamino)-2-styrylquinazolin-4(3H)-ones:
synthesis of 1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-ones
oxidative
C−H
amination
of
a
metal-free
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Yetong Zhang, Yinlin Shao,* Julin Gong, Jianghe Zhu, Tianxing Cheng, and Jiuxi
Chen*
College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, China.
O
N
Ar
O
N
Ar
N
cat. (PhSe)2
NH
N
N
R1
Ph
R
Oxidant
metal-free
Ph
23 examples
up to 87% yield
ABSTRACT: A novel metal-free catalysis protocol for the synthesis of
1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-ones via intramolecular oxidative C-H
amination of (E)-3-(arylamino)-2-styrylquinazolin-4(3H)-ones has been developed
with moderate to good yield. The method shows good functional group tolerance. The
presented approach offers a new synthetic pathway toward the core structures of
2,3-fused quinazolinones. Moreover, the present synthetic route could be readily
scaled up to gram quantity without difficulty. A possible mechanism involves
seleniranium ion followed by three-membered ring opening to form C-N bond.
_______________________________________________________________________________
INTRODUCTION
Among the numerous nitrogen-containing compounds, 2,3-fused quinazolinones with
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diverse heterocycles represents an important scaffold ubiquitously found in many
natural products, drugs, agrochemicals and other pharmaceutically active ingredients
(eg. tryptanthrin and rutaecarpine),1 they are known to exhibit antibiotic, anticancer
and antimalarial activities (Fig. 1).2 In view of their importance, a series of methods
has been developed for the construction of these 2,3-heterocycles-fused
quinazolinones.3
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Fig.1 Bioactive 2,3-heterocycle fused quinazolinones
CF3
O
N
O
N
N
O
N
F
N
N
N
N
N
N
N
Ph
Anti cancer
O
PED4 inhibitor
O
Antimicrobial
O
N
N
N
N
COOH
N
S
N
H
O
OCH3
Antiallergic
EGFR inhibitor
The combined molecules of indazole and quinazolinone frameworks,
indazoloquinazolinone derivatives, are important biological molecules, some of them
are potent inhibitors of phosphodiesterase 4 (PDE4)4a and specificity against cancer
cells.4b Our group developed three strategies for the construction of the
indazolo[3,2-b]quinazolinones via copper-catalyzed coupling reaction5a-b or
palladium-catalyzed sequential cyclization/C−H activation cascade reaction.5c
Recently,
we
reported
palladium-catalyzed
synthesis
of
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indazolo[3,2-b]quinazolinones which were further proved to be potential as a new
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class of small-molecule blue fluorophores for fluorescent materials involving
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intramolecular
aerobic
oxidative
C–H
amination
of
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2-aryl-3-(arylamino)quinazolinones (Scheme 1a).5d Moreover, the combined
molecules of pyrazole and quinazolinone skeletons, pyrazolo[5,1-b]quinazolinones,
are important biological molecules which exhibit a broad spectrum of activities such
as antiallergic,6a antimicrobial activity.6b Traditionally, pyrazolo[5,1-b]quinazolinone
structures are constructed by the condensation of isatoic anhydride with pyrazolone,
which is limited in scope and inconvenient operation.6 Wang group reported
transition-metal catalyzed synthesis of pyrazolo[5,1-b]quinazolinone derivatives.7
Although the transition-metal-catalyzed strategies that have shown high efficiency,
metal-free protocols are also desirable due to their advantages with regard to purity
requirements in biological and medicinal research.8 Organoselenium catalysis is an
important and unique subject that presents additional opportunities to develop novel
green synthetic methods with industrial potential compared with transition metals.9
Also selenium is much less expensive than noble metals, and the organoselenium
catalysts are sufficiently robust to be recycled and reused with little deactivation.10
Recently, organoselenium catalysts have been successfully employed in a series of
useful transformations.11 Since Breder’s pioneering contributions to the direct
oxidative vinylic amination of alkenes by selenium catalysis,12 remarkable advances
in selenium-catalyzed C=C functionalization have been documented. In continuation
of our interest on N-heterocycles synthesis,13 we herein report the first example of
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metal-free method for the synthesis of pyrazolo[5,1-b]quinazolinones through
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selenium-catalyzed
oxidative
C−H
amination
of
easily
available
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9
(E)-3-(arylamino)-2-styrylquinazolin-4(3H)-ones (Scheme 1b).
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Scheme 1. The new strategy for the synthesis of pyrazolo[5,1-b]quinazolinones
a) Pd-catalyzed synthesis of indazolo[3,2-b]quinazolinones
Ar
O
O
N
Ar
N
NH
[Pd]
N
H
N
R1
R
R
ref. 5d
Our previous work
N
R1
b) Selenium-catalyzed synthesis of pyrazolo[5,1-b]quinazolinones (This work)
O
Ar
O
Ar
N
cat. (PhSe)2
NH
N
N
R1
Ph
R
Oxidant
N
Ph
N
metal-free
RESULTS AND DISCUSSION
At
the
outset
of
our
studies,
we
used
(E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1a) as the test substrate to
determine optimal conditions for the title reaction. In initial experiments 1a was
reacted with 2 equivalent of N-Fluorobenzenesulfonimide (NFSI) in the presence of
o
various catalysts in toluene at 110 C for 48 h. The reaction did not work in the
absence of any catalyst (Table 1, entry 1). However, diphenyl diselane as a catalyst
provided access to target structure 1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one
(2a) in 49% yield (Table 1, entry 2), while 1,2-dibenzyldisulfane (DBDS) furnished
the oxidative amination product 2a only in 17% (Table 1, entry 3). Replacement of
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diphenyl diselane with other common transition metal catalysts, such as PdCl2 or
FeCl3, was ineffective (Table 1, entries 4−5). A survey of solvent revealed that
acetonitrile was optimal to give a best 79% yield, and the use of dimethyl sulfoxide
(DMSO), N,N-dimethylformamide (DMF), xylene and pyridine led to lower yields
(Table 1, entries 6−10). Encouraged by the promising result, we further examined the
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o
reaction temperature and found 90 C was enough for such oxidative/cyclization
process (Table 1, entries 11−12). The yield of the desired product decreased when the
reaction time was shortened to 24 h (Table 1, entry 11). The classical oxidants such as
K2S2O8, 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ) and Cu(OAc)2 diminished the
yield of 2a sharply (Table 1, entries 13−15). The yield decreased to some extent by
either removing 4 Å molecular sieves from the reaction medium or decreasing the
amount of oxidant to 1.0 equivalent (Table 1, entries 16-17). Therefore, the optimal
reaction conditions can be summarized as follows: 0.2 mmol substrate in acetonitrile
(5 mL) with PhSeSePh catalyst (5 mol %), NFSI (2 equiv) and 4 Å molecular sieves
0.06 g at 90 °C for 48 h under air atmosphere. The structure of 2a was further
confirmed by X-ray diffraction analysis (Fig. 2)14.
Fig.2 X-ray crystal structure of product 2a.
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Table 1. Optimization of reaction conditionsa
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O
N
O
Ph
N
H
N
catalyst, oxidant
solvent
N
Ph
N
Ph
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Ph
N
1a
2a
temp. (oC)
yield (%)b
entry
catalyst
oxidant
solvent
1
-
110
110
110
110
110
110
110
110
110
110
90
Toluene
Toluene
Toluene
Toluene
Toluene
DMF
trace
49
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
NFSI
K2S2O8
DDQ
2
(PhSe)2
DBDS
3
17
4
PdCl2
trace
trace
41
5
FeCl3
6
(PhSe)2
(PhSe)2
(PhSe)2
(PhSe)2
(PhSe)2
(PhSe)2
(PhSe)2
(PhSe)2
(PhSe)2
(PhSe)2
(PhSe)2
(PhSe)2
7
DMSO
14
8
xylene
49
9
Pyridine
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
trace
10
79
c
11
79
65
5
(70)
12
70
13
90
14
90
35
4
15
16d
17e
90
Cu(OAc)2
NFSI
NFSI
90
65
70
90
a
1a
Conditions:
(0.2 mmol), catalyst (5 mol%), oxidant (2 equiv), solvent (5 mL),
4A MS (0.06 g), 90 oC, 48 h. bIsolated yield. c24 h. d1.0 eq.NFSI was used.
ewithout 4A MS.
With optimized conditions in hand, investigations continued with the exploration of
the scope of our oxidative amination/cyclization protocol for the construction of
pyrazolo[5,1-b]quinazolinones (Table 2). A variety of substituents (R1, R2, R3) in
compound 1 were tested and delivered to product 2 in uniformly high efficiency.
First,
the
variation
of
the
R1
group
of
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(E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-ones 1 was investigated. The results
showed that both electron-donating and electron-withdrawing substituents were
well-tolerated and provided the corresponding products in moderate to good yields.
For example, substrates bearing a methyl group afforded the cyclized products 2b, 2c
and 2d in 80-85% yield, respectively (Table 2, entries 1-3). Substrate
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(E)-7,8-dimethyl-3-(phenylamino)-2-styrylquinazolin-4(3H)-one
afforded
the
corresponding desired product 2e in 82% yield similarly (Table 2, entry 4).
Electron-donating group such as -OMe at the 6 position of the aryl ring in
quinazolinone furnished product 2f in 87% yield. To our delight, the method tolerates
the entire range of halogen substituents and strong electron-withdrawing substituent
(e.g., -CF3), although the yield of cyclized products 2g-2n were slight lower than
those of electron-sufficient substrates, which makes this method particularly
appealing, enabling further access to more complex compounds in combination with
cross-coupling transformations (Table 2, entries 6−13).
We next examined the substitution effect of R2 on the aromatic ring of
(E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-ones. Substrates bearing an o-, m- or
p-methyl substituent attaching to the amino group were evaluated, affording 2o-2q in
67-82% yield respectively (Table 2, entries 14−16). The lower yield of 2o may arise
from the steric hindrance. The electronic property of the substituents is not critical for
this transformation. In general, the substrates bearing an electron-donating substituent
(eg. −OMe) provided
a
slightly higher yield than those bearing an
electron-withdrawing substituent e.g. −F, −Cl and −CF3 (Table 2, entries 17−22).
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Encouraged by the promising result, we further examined the variation of aryl group
in styrene motif of (E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-ones (Table 2,
entries 23−25). It is obvious that electron-withdrawing groups decreased the
cyclization yield to some extent, probably due to the decreasing activity to form active
electrophilic additional intermediate with Se species. Alkyl substituents such as
isopropyl on the nitrogen atom was also fine compatible with this intramolecular
oxidative amination cyclization reaction (Table 2, entries 26).
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Table 2. Synthesis of 1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-onesa
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R2
R2
O
N
O
N
5
6
7
8
R3
NH
PhSeSePh, NFSI
N
N
N
R1
R1
o
MS 4A, MeCN, 90 oC, 48 h
R3
1
2
9
(1)
(2)
(3)
(4)
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O
O
O
N
O
N
N
N
N
N
N
N
N
N
N
N
2b,
2c,
2d,
2e,
82%
85%
83%
80%
(5)
(6)
(7)
(8)
Cl
O
O
O
O
F
N
N
N
H3CO
N
N
N
N
N
N
F
N
N
N
2f,
2g,
2h,
2i,
87%
70%
65%
71%
(9)
(10)
(11)
(12)
O
O
O
O
Cl
Br
I
N
N
N
N
N
N
N
N
N
Cl
N
N
N
2j,
2k,
2l
2m,
71%
70%
69%
78%
(13)
(14)
(15)
(16)
O
O
O
O
F3C
N
N
N
N
N
N
N
N
N
N
N
N
2n,
2o,
2p,
2q,
80%
60%
67%
82%
OCH3
Cl
(17)
(21)
(25)
(18)
(19)
(20)
Cl
O
O
O
O
Cl
N
N
N
N
N
N
N
N
N
N
N
N
2r,
2s,
2t,
2u,
85%
55%
70%
66%
F
CF3
(22)
(23)
(24)
O
F
O
N
O
O
N
N
N
N
N
N
N
OCH3
N
N
N
F
N
2y
, 29 %
2x
, 85 %
2v,
2w,
62%
65%
(26)
O
O
N
N
N
N
N
Cl
N
Cl
2za
, 79 %
2z
, trace
Conditions: (0.2 mmol), (PhSe)2 (5 mol %), NFSI (2 equiv), CH3CN (5 mL), MS 4A (0.06 g), 90 oC, 48 h, isolated yield.
a
1
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The present synthetic route to pyrazolo[5,1-b]quinazolinone derivatives could be
readily scaled up to gram quantity without difficulty. For instance, the reaction at the
3 mmol scale afforded the corresponding product 2a in 78% isolated yield. In
addition, N-methylation of 2a gave pyrazolo[5,1-b]quinazolin-4-ium iodide 3a in
95% yield (Scheme 2). Furthermore, the structure of 3a was confirmed by X-ray
diffraction analysis (Fig. 3).14
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Scheme 2 Gram-scale synthesis of 2a and subsequent methylation
O
O
PhSeSePh (5 mol%)
NFSI (2 eq), MS 4Å
MeCN, 90 oC, 36 h
78% yield
O
N
N
CH3I (12.5 equiv)
N
N
I
NH
N
Ph
N
Ph
THF, 70 oC, 24 h
95% yield
N
N
Ph
CH3
3a
3 mmol, 1.017g
0.789 g
Fig. 3 X-ray crystal structure of product 3a.
Scheme 3 Control experiments
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O
N
O
N
PhSeSePh (5 mol%)
NH
N
N
(a)
N
o
MS 4A, MeCN, 90 oC, 48 h
9
2a
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1a
O
N
O
N
N
N
NFSI (2 equiv)
N
(b)
+
PhSeSePh
(1 equiv)
N
o
MS 4A, MeCN, 90 oC, 48 h
Se
50% yield
4a
5a
To gain insight into the diphenyl diselane-catalyzed oxidative amination cyclization
reaction mechanism, further experiments were performed (Scheme 3). Our initial
attempts to perform the reaction in the absence of NFSI failed to give the desired
product 2a (Scheme 3a). However, (Z)-3-(Methyl(phenyl)amino)-2-(2-phenyl-1-
(phenylselanyl)vinyl)-quinazolin-4(3H)-one (5a) was obtained in 50% yield when
(E)-3-(methyl(phenyl)amino)-2-styrylquinazolin-4(3H)-one (4a) was reacted with
stoichiometric PhSeSePh under standard conditions (Scheme 3b), indicating that an
intermolecular electrophilic addition of Se species with C=C bonds may occur in this
catalytic transformation.
A plausible mechanism for this diphenyl diselane-catalyzed oxidative amination
cyclization reaction is shown in Scheme 4. First, NFSI undergoes nucleophilic attack
by diphenyl diselane leading to cationic species I. Subsequent electrophilic addition to
the C=C double of 1 gives rise to seleniranium ion II, and then intramolecular attack
of the amino group leads to three-membered ring opening to yield intermediate III.
Which in turn undergoes elimination of HF and HN(SO2Ph)2 together with removal of
the catalyst to complete the catalytic cycle.
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Scheme 4 Proposed mechanism.
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NFSI
2a
HF + HN(SO2Ph)2 +
PhSeSePh
9
O
Ph
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N
N
Ph
F
Ph
Se
N
Se
Ph
F
Se
Ph
Ph
Se
N(SO2Ph)2
N(SO2Ph)2
O
N
I
III
NHPh
Se
N
1a
Ph
Ph
F
Ph
Se
N(SO2Ph)2
II
CONCLUSIONS
In summary, we have developed a new approach for the synthesis of
1,2-diarylpyrazolo[5,1-b]quinazolin-9(1H)-ones by the diphenyl diselane-catalyzed
intramolecular
oxidative
amination
cyclization
reaction
of
(E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-ones. This protocol provides an
alternative synthetic pathway to access 2,3-heterocycles-fused quinazolinones.
Further studies on the other bioactivities of the pyrazolo[5,1-b]quinazolinones and the
construction of other useful N-heterocycles are underway in our laboratory.
EXPERIMENTAL SECTION
General Methods. Melting points are uncorrected. 1H NMR and 13C NMR spectra
were measured on a 500 MHz spectrometer (1H at 500 MHz, 13C at 125 MHz), using
CDCl3 and d6-DMSO as the solvent at room temperature. Chemical shifts are given δ
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relative to TMS, and the coupling constants J are given in hertz. High-resolution mass
spectra were recorded on an ESI-Q-TOF mass spectrometer. All
(E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-one substrates (1a-1w) were prepared
by the modified literature methods.15 Other commercially obtained reagents were used
without further purification. Column chromatography was performed using EM silica
gel 60 (300−400 mesh). X-ray crystallographic analysis was done at the X-ray
crystallography facility, Shanghai Institute of Organic Chemistry (SIOC), Chinese
Academy of Sciences (CAS).
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General
procedure
for
the
Synthesis
of
1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-ones.
To a Schlenk tube were added (E)-3-(phenylamino)-2-styrylquinazolin-4(3H)-one 1
(0.2 mmol), (PhSe)2 (0.01 mmol), NFSI (0.4 mmol), MS 4Å (60 mg) and MeCN (5
mL) under air. The tube was tightly capped and stirred for 10 minutes at room
temperature for proper mixing of the reactants, and then heated at 90 °C with vigorous
stirring for 48 hours. Then the mixture was poured into 10 mL water, extracted with
ethyl acetate (10 mL X 3), the combined organic layers were dried over anhydrous
Na2SO4 and filtrated. The solvent was evaporated under vacuum and the residue was
purified by flash column chromatography with petroleum ether/ethyl acetate (4:1) to
afford the desired products.
(E)-3-(Phenylamino)-2-styrylquinazolin-4(3H)-one (1a): white solid (2.7 g, 80%).
1H NMR (500 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.12-8.05 (m, 2H), 7.91-7.80 (m, 2H),
7.63 (d, J = 6.5 Hz, 2H), 7.55-7.40 (m, 5H), 7.21 (t, J = 7.5 Hz, 2H), 6.86 (t, J = 7.0
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Hz, 1H), 6.71 (d, J = 8.0 Hz, 2H); C{1H} NMR (125 MHz, CDCl3) δ 160.1, 154.0,
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147.2, 146.8, 140.3, 135.0, 134.9, 129.8, 129.2, 129.0, 127.7, 127.4, 126.5, 126.3,
121.1, 120.5, 118.2, 112.8. HRMS (ESI) calcd for C22H18N3O1 [M+H]+: 340.1450,
found 340.1454.
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(E)-5-Methyl-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1b): white solid (1.50
g, 85%). IR (KBr) v (cm-1): 3267, 3022, 2972, 1658, 1633, 1599, 1551, 1494, 1475,
1447, 1354, 811, 755, 698. 1H NMR (500 MHz, DMSO-d6) δ 9.11 (s, 1H), 8.04 (d, J
= 16 Hz, 1H), 7.71 (s, 1H), 7.62 (d, J = 8.0 Hz, 3H), 7.44-7.39 (m, 4H), 7.28 (d, J =
7.5 Hz, 1H), 7.20 (t, J = 8.0 Hz, 2H), 6.85 (s, 1H), 6.71 (d, J = 8.0 Hz, 2H), 2.73 (s,
13
3H); C{1H} NMR (125 MHz, CDCl3) δ 161.7, 153.1, 149.0, 146.9, 141.5, 141.4,
135.8, 134.0, 129.8, 129.7, 129.2, 128.9, 128.2, 126.1, 122.9, 119.7, 118.4, 114.7,
22.9. HRMS (ESI) calcd for C23H20N3O1 [M+H]+: 354.1601, found 354.1609.
(E)-6-Methyl-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1c): white solid (1.50
g, 85%). IR (KBr) v (cm-1): 3257, 3040, 2982, 1660, 1626, 1597, 1545, 1489, 1444,
1358, 1342, 827, 774, 692. 1H NMR (500 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.02 (d, J
= 16 Hz, 1H), 7.90 (s, 1H), 7.71 (s, 2H), 7.62-7.61 (m, 2H), 7.47-7.37 (m, 4H),
7.21-7.18 (m, 2H), 6.85 (t, J = 7.5 Hz, 1H), 6.68 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 160.4, 151.7, 145.7, 144.6, 140.1, 135.9, 135.5,
134.8, 128.8, 128.6, 127.9, 127.2, 126.6, 125.5, 122.0, 119.9, 117.3, 113.8, 20.5.
HRMS (ESI) calcd for C23H20N3O1 [M+H]+: 354.1601, found 354.1603.
(E)-7,8-Dimethyl-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1e): white solid
(1.56 g, 85%). IR (KBr) v (cm-1): 3254, 3056, 1661, 1629, 1603, 1550, 1495, 1447,
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1360, 1339, 783, 755, 691. 1H NMR (500 MHz, CDCl3) δ 8.20 (d, J = 15.5 Hz, 1H),
7.98 (d, J = 8.0 Hz, 1H), 7.60-7.55 (m, 3H), 7.38-7.34 (m, 3H), 7.26-7.22 (m, 4H),
6.98 (t, J = 7.5 Hz, 1H), 6.80 (d, J = 8.0 Hz, 2H), 2.71 (s, 3H), 2.46 (s, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 161.5, 151.6, 146.7, 145.4, 143.8, 141.0, 135.8, 134.1,
129.6, 129.4, 128.8, 128.6, 128.1, 123.8, 122.7, 119.0, 118.5, 114.6, 21.0, 13.2.
HRMS (ESI) calcd for C24H22N3O1 [M+H]+: 368.1763, found 368.1763.
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(E)-6-Methoxy-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1f): white solid
(1.48 g, 80%). IR (KBr) v (cm-1): 3268, 3024, 2976, 1662, 1632, 1599, 1549, 1491,
1439, 1339, 822, 769, 690. 1H NMR (500 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.99 (d, J
= 16.0 Hz, 1H), 7.76 (d, J = 8.5 Hz, 1H), 7.60 (d, J = 7.0 Hz, 2H), 7.51-7.37 (m, 6H),
7.20 (t, J = 8.0 Hz, 2H), 6.85 (t, J = 7.5 Hz, 1H), 6.69 (d, J = 8.0 Hz, 2H), 3.88 (s,
13
3H); C{1H} NMR (125 MHz, CDCl3) δ 161.3, 158.3, 151.3, 146.7, 142.3, 140.6,
135.9, 129.7, 129.6, 129.5, 128.9, 128.1, 125.4, 123.0, 121.9, 118.3, 114.8, 106.3,
56.0. HRMS (ESI) calcd for C23H20N3O2 [M+H]+: 370.1566, found 370.1560.
(E)-6-Fluoro-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1g): white solid (1.55
g, 87%). IR (KBr) v (cm-1): 3261, 3039, 1660, 1628, 1602, 1548, 1483, 1445, 1344,
1
832, 777, 690. H NMR (500 MHz, DMSO-d6) δ 9.24 (s, 1H), 8.05 (d, J = 16.0 Hz,
1H), 7.87 (d, J = 5.0 Hz, 1H), 7.80-7.77 (m, 2H), 7.63-7.61 (m, 2H), 7.47-7.39 (m,
13
4H), 7.22-7.19 (m, 2H), 6.87 (d, J = 7.5 Hz, 1H), 6.72 (d, J = 8.0 Hz, 2H); C{1H}
NMR (125 MHz, CDCl3) δ 161.7, 152.8, 146.4, 144.3, 141.7, 135.6, 130.3 (d, J = 8.3
Hz), 130.0, 129.7, 129.0, 128.3, 123.6 (d, J = 24.2 Hz), 123.2, 117.9, 114.8, 111.9 (d,
J = 23.8 Hz). HRMS (ESI) calcd for C22H17F1N3O1 [M+H]+: 358.1356, found
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358.1360.
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(E)-7-Fluoro-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1h): white solid (1.52
g, 85%). IR (KBr) v (cm-1): 3263, 3042, 1667, 1619, 1579, 1546, 1476, 1443, 1344,
867, 774, 699. 1H NMR (500 MHz, DMSO-d6) δ 9.24 (s, 1H), 8.18-8.15 (m 1H), 8.08
(d, J = 16.0 Hz, 1H), 7.64-7.56 (m, 3H), 7.48-7.38 (m, 5H), 7.21 (t, J = 8.0 Hz, 2H),
6.86 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 8.5 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ
160.7, 154.7, 146.5, 142.6, 135.5, 130.2, 129.7, 129.7, 129.0, 128.4, 123.5, 117.9,
116.5, 115.4 (d, J = 23.8 Hz), 114.8, 112.9 (d, J = 21.8 Hz). HRMS (ESI) calcd for
C22H17F1N3O1 [M+H]+: 358.1356, found 358.1361.
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(E)-5-Chloro-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1i): white solid (1.62
g, 87%). IR (KBr) v (cm-1): 3268, 3055, 1672, 1628, 1581, 1542, 1496, 1450, 1346,
1
814, 753, 693. H NMR (500 MHz, DMSO-d6) δ 9.24 (s, 1H), 8.11-8.06 (m, 2H),
7.86 (d, J = 2.0 Hz, 1H), 7.64-7.62 (m, 2H), 7.57-7.55 (m, 1H), 7.48-7.40 (m, 4H),
13
7.21 (t, J = 8.0 Hz, 2H), 6.86 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 8.0 Hz, 2H); C{1H}
NMR (125 MHz, CDCl3) δ 160.9, 154.7, 148.5, 146.4, 142.6, 141.2, 135.5, 130.2,
129.7, 129.0, 128.5, 128.4, 127.3, 127.1, 123.2, 119.5, 117.8, 114.8. HRMS (ESI)
calcd for C22H17Cl1N3O1 [M+H]+: 374.1060, found 374.1066.
(E)-6-Chloro-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1j): white solid (1.48
g, 88%). IR (KBr) v (cm-1): 3265, 3032, 1678, 1635, 1604, 1542, 1496, 1471, 1335,
1
831, 754, 669. H NMR (500 MHz, DMSO-d6) δ 9.27 (s, 1H), 8.09-8.04 (m, 2H),
7.93-7.90 (m, 1H), 7.82 (d, J = 9.0 Hz, 1H), 7.64-7.62 (m, 2H), 7.47-7.39 (m, 4H),
13
7.21 (t, J = 8.0 Hz, 2H), 6.86 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 8.5 Hz, 2H); C{1H}
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NMR (125 MHz, CDCl3) δ 160.5, 153.7, 146.3, 146.1, 142.2, 135.6, 135.4, 132.3,
130.1, 129.7, 129.5, 129.0, 128.3, 126.4, 123.2, 122.1, 117.9, 114.8. HRMS (ESI)
calcd for C22H17Cl1N3O1 [M+H]+: 374.1060, found 374.1069.
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(E)-6-Bromo-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1l): white solid (1.81
g, 87%). IR (KBr) v (cm-1): 3266, 3030, 1676, 1635, 1601, 1541, 1496, 1468, 1333,
1
829, 751, 691. H NMR (500 MHz, DMSO-d6) δ 9.25 (s, 1H), 8.18 (d, J = 2.0 Hz,
1H), 8.09-8.01 (m, 2H), 7.75 (d, J = 9.0 Hz, 1H), 7.63-7.62 (m, 2H), 7.47-7.40 (m,
4H), 7.20 (t, J = 8.0 Hz, 2H), 6.86 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 8.0 Hz, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 160.3, 153.9, 146.4, 146.3, 142.3, 138.1, 135.5,
130.1, 129.7, 129.6, 129.6, 129.0, 128.3, 123.2, 122.4, 120.0, 117.9, 114.8. HRMS
(ESI) calcd for C22H17Br1N3O1 [M+H]+: 418.0555, found 418.0557.
(E)-6-Iodo-3-(phenylamino)-2-styrylquinazolin-4(3H)-one (1m): white solid (1.97
g, 85%). IR (KBr) v (cm-1): 3263, 3059, 1671, 1629, 1602, 1541, 1495, 1464, 1331,
1
830, 756, 691. H NMR (500 MHz, DMSO-d6) δ 9.25 (s, 1H), 8.37 (d, J = 2.0 Hz,
1H), 8.17-8.06 (m, 2H), 7.63-7.58 (m, 3H), 7.46-7.40 (m, 4H), 7.20 (t, J = 8.0 Hz,
13
2H), 6.86 (t, J = 7.5 Hz, 1H), 6.71 (d, J = 8.0 Hz, 2H); C{1H} NMR (125 MHz,
CDCl3) δ 160.1, 154.1, 146.3, 143.7, 142.4, 135.9, 135.5, 130.2, 129.7, 129.6, 129.0,
128.3, 123.2, 122.7, 117.9, 114.8, 100.1. HRMS (ESI) calcd for C22H17I1N3O1
[M+H]+: 466.0416, found 466.0410.
(E)-3-(Phenylamino)-2-styryl-6-(trifluoromethyl)quinazolin-4(3H)-one (1n): white
solid (1.63 g, 80%). IR (KBr) v (cm-1): 3274, 3042, 1677, 1629, 1603, 1546, 1495,
1
1451, 1299, 846, 761, 691. H NMR (500 MHz, CDCl3) δ 8.50 (s, 1H), 8.25 (d, J =
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6
7
13
2H), 7.01 (t, J = 7.5 Hz, 1H), 6.82 (d, J = 8.0 Hz, 2H); C{1H} NMR (125 MHz,
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9
CDCl3) δ 160.7, 155.4, 149.5, 146.1, 143.2, 135.2, 130.9, 130.3, 129.6, 128.9, 128.6,
128.1 (d, J = 33.5 Hz), 124.9, 124.9 (d, J = 4.1 Hz), 123.7 (d, J = 272.3 Hz), 123.1,
120.7, 117.5, 114.7. HRMS (ESI) calcd for C23H17F3N3O1 [M+H]+: 408.1324, found
408.1322.
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(E)-2-Styryl-3-(o-tolylamino)quinazolin-4(3H)-one (1o): white solid (1.41 g, 80%).
IR (KBr) v (cm-1): 3333, 3071, 1683, 1634, 1608, 1548, 1471, 1449, 1339, 820, 755,
1
698. H NMR (500 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.12-8.06 (m, 2H), 7.90 (t, J =
8.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 6.5 Hz, 2H), 7.54 (t, J = 7.5 Hz,
1H), 7.48 (d, J = 16.0 Hz, 1H), 7.43-7.39 (m, 3H), 7.17 (d, J = 7.5 Hz, 1H), 6.95 (t, J
= 8.0 Hz, 1H), 6.79 (t, J = 7.5 Hz, 1H), 6.20 (d, J = 8.0 Hz, 1H), 2.41 (s, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 160.1, 154.1, 146.3, 143.7, 142.4, 135.9, 135.5, 130.2,
129.7, 129.6, 129.0, 128.3, 123.2, 122.7, 117.9, 114.8, 100.1. HRMS (ESI) calcd for
C23H20N3O1 [M+H]+: 354.1606, found 354.1600.
(E)-2-Styryl-3-(m-tolylamino)quinazolin-4(3H)-one (1p): white solid (1.46 g, 83%).
IR (KBr) v (cm-1): 3243, 3078, 1658, 1631, 1609, 1548, 1468, 1448, 1341, 823, 779,
1
693. H NMR (500 MHz, DMSO-d6) δ 9.13 (s, 1H), 8.12-8.05 (dd, 2H), 7.89 (t, J =
8.0 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.53 (t, J = 7.5 Hz,
1H), 7.48-7.39 (m, 4H), 7.08 (t, J = 8.0 Hz, 1H), 6.67 (d, J = 7.5 Hz, 1H), 6.54 (s,
1H), 6.48 (d, J = 8.0 Hz, 1H), 2.20 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
160.1, 154.1, 146.3, 143.7, 142.4, 135.9, 135.5, 130.2, 129.7, 129.6, 129.0, 128.3,
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123.2, 122.7, 117.9, 114.8, 100.1. HRMS (ESI) calcd for C23H20N3O1 [M+H]+:
354.1606, found 354.1599.
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(E)-2-Styryl-3-(p-tolylamino)quinazolin-4(3H)-one (1q): white solid (1.43 g, 82%).
IR (KBr) v (cm-1): 3253, 3026, 1682, 1634, 1609, 1546, 1467, 1448, 1339, 873, 786,
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695. H NMR (500 MHz, CDCl3) δ 8.23-8.15 (m, 2H), 7.80-7.79 (m, 2H), 7.60-7.57
(m, 3H), 7.46-7.43 (m, 1H), 7.36 (d, J = 8.0 Hz, 3H), 7.15 (s, 1H), 7.05 (d, J = 8.5 Hz,
2H), 6.73 (d, J = 8.5 Hz, 2H), 2.25 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
161.4, 153.5, 147.6, 144.2, 141.6, 135.7, 134.9, 132.6, 130.2, 129.9, 129.0, 128.3,
127.8, 127.1, 126.5, 121.2, 118.4, 115.0, 20.8. HRMS (ESI) calcd for C23H20N3O1
[M+H]+: 354.1606, found 354.1611.
(E)-3-((4-Methoxyphenyl)amino)-2-styrylquinazolin-4(3H)-one (1r): white solid
(1.57 g, 85%). IR (KBr) v (cm-1): 3253, 3026, 2832, 1678, 1631, 1605, 1545, 1469,
1
1448, 1332, 823, 758, 698. H NMR (500 MHz, CDCl3) δ 8.24-8.16 (m, 2H),
7.82-7.77 (m, 2H), 7.63-7.59 (m, 3H), 7.45-7.42 (m, 1H), 7.39-7.35 (m, 3H), 7.21 (s,
1H), 6.82-6.78 (m, 4H), 3.72 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 161.3,
155.8, 153.3, 147.4, 141.4, 139.8, 135.6, 134.7, 129.8, 128.8, 128.1, 127.6, 126.9,
126.4, 121.0, 118.3, 116.6, 114.8, 55.6. HRMS (ESI) calcd for C23H20N3O2 [M+H]+:
370.1556, found 370.1559.
(E)-3-((2-Chlorophenyl)amino)-2-styrylquinazolin-4(3H)-one (1s): white solid
(1.49 g, 80%). IR (KBr) v (cm-1): 3318, 3060, 1689, 1633, 1607, 1548, 1471, 1449,
1
1334, 823, 758, 698. H NMR (500 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.11-8.05 (m,
2H), 7.90 (t, J = 8.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 7.0 Hz, 2H), 7.54
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(t, J = 7.5 Hz, 1H), 7.46-7.39 (m, 5H), 7.10 (t, J = 8.0 Hz, 1H), 6.90 (t, J = 8.0 Hz,
1H), 6.49 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.9, 153.6,
147.5, 142.8, 142.1, 135.6, 135.1, 130.1, 130.0, 129.0, 128.3, 128.1, 127.9, 127.2,
126.7, 123.3, 121.3, 121.2, 117.7, 114.0. HRMS (ESI) calcd for C22H17Cl1N3O1
[M+H]+: 374.1060, found 374.1062.
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(E)-3-((3-Chlorophenyl)amino)-2-styrylquinazolin-4(3H)-one (1t): white solid
(1.56 g, 84%). IR (KBr) v (cm-1): 3242, 3079, 1667, 1632, 1607, 1548, 1469, 1448,
1
1342, 856, 782, 696. H NMR (500 MHz, DMSO-d6) δ 9.44 (s, 1H), 8.12-8.05 (m,
2H), 7.90 (t, J = 8.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 7.0 Hz, 2H), 7.54
(t, J = 7.5 Hz, 1H), 7.45-7.39 (m, 4H), 7.22 (t, J = 8.0 Hz, 1H), 6.89 (d, J = 8.5 Hz,
1H), 6.80 (s, 1H), 6.65 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ
161.3, 153.2, 147.9, 147.5, 142.1, 135.6, 135.1, 130.8, 130.1, 129.0, 128.3, 127.9,
127.1, 126.7, 123.2, 121.0, 120.3, 117.7, 114.9, 112.8. HRMS (ESI) calcd for
C22H17Cl1N3O1 [M+H]+: 374.1060, found 374.1062.
(E)-3-((4-Chlorophenyl)amino)-2-styrylquinazolin-4(3H)-one (1u): white solid
(1.62 g, 87%). 1H NMR (500 MHz, DMSO-d6) δ 9.37 (s, 1H), 8.12-8.04 (m, 2H), 7.89
(d, J = 7.0 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 6.5 Hz, 2H), 7.54 (d, J = 7.5
Hz, 1H), 7.45-7.39 (m, 4H), 7.24 (d, J = 9.0 Hz, 2H), 6.74 (d, J = 9.0 Hz, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 161.3, 153.2, 147.5, 145.2, 142.0, 135.6, 135.1,
130.1, 129.7, 129.0, 128.3, 128.2, 127.9, 127.1, 126.7, 121.0, 117.8, 116.1. HRMS
(ESI) calcd for C22H17Cl1N3O1 [M+H]+: 374.1060, found 374.1062.
(E)-3-((4-Fluorophenyl)amino)-2-styrylquinazolin-4(3H)-one (1v): white solid
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(1.53 g, 86%). IR (KBr) v (cm-1): 3244, 3022, 1668, 1633, 1608, 1548, 1469, 1448,
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1341, 829, 755, 695. H NMR (500 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.11-8.05 (m,
8
9
2H), 7.89 (t, J = 7.5 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 7.0 Hz, 2H),
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7.54-7.39 (m, 5H), 7.04 (t, J = 9.0 Hz, 2H), 6.76-6.73 (m, 2H); C{1H} NMR (125
MHz, CDCl3) δ 161.4, 153.2, 147.5, 142.6, 141.9, 135.6, 135.0, 130.0, 129.0, 128.2,
127.9, 127.1, 126.7, 121.0, 118.0, 116.5, 116.3 (d, J = 22.9 Hz). HRMS (ESI) calcd
for C22H17F1N3O1 [M+H]+: 358.1356, found 358.1360.
(E)-2-Styryl-3-((4-(trifluoromethyl)phenyl)amino)quinazolin-4(3H)-one (1w): white
solid (1.70 g, 84%). IR (KBr) v (cm-1): 3259, 3087, 1678, 1633, 1618, 1545, 1466,
1448, 1332, 831, 774, 695. 1H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.13-8.06
(m, 2H), 7.91 (t, J = 8.5 Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H), 7.65 (d, J = 7.0 Hz, 2H),
7.55 (d, J = 8.0 Hz, 3H), 7.42 (d, J = 16.5 Hz, 4H), 6.88 (d, J = 8.0 Hz, 2H); 13C{1H}
NMR (125 MHz, CDCl3) δ 161.4, 153.2, 147.5, 142.6, 141.9, 135.6, 135.0, 130.0,
129.0, 128.2, 127.9, 127.1 (d, J = 4.4 Hz), 126.7, 121.0, 118.0, 116.5, 116.4, 116.2.
HRMS (ESI) calcd for C23H17F3N3O1 [M+H]+: 408.1324, found 408.1330.
(E)-2-(4-Methoxystyryl)-3-(phenylamino)quinazolin-4(3H)-one (1x): Pale-yellow
solid (1.47 g, 80%). IR (KBr) v (cm-1): 3253, 3022, 1685, 1633, 1603, 1543, 1470,
1
1445, 1338, 827, 773, 690. H NMR (500 MHz, CDCl3) δ 8.21 (d, J = 7.5 Hz, 2H),
7.80 (m, 2H), 7.55 (d, J = 8.5 Hz, 2H), 7.44–7.41 (m, 2H), 7.26-7.22 (m, 3H), 7.00 (t,
J = 7.5 Hz, 1H), 6.88 (d, J = 8.5 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 3.83 (s, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 161.3, 154.0, 146.4, 134.9, 129.9, 129.5, 128.3,
127.0, 126.3, 122.9, 120.6, 114.7, 114.3, 55.4. HRMS (ESI) calcd for C23H20N3O2
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[M+H]+: 370.1550, found 370.1555.
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(E)-2-(2,5-Difluorostyryl)-3-(phenylamino)quinazolin-4(3H)-one (1y): Pale-yellow
solid (1.50 g, 80%). IR (KBr) v (cm-1): 3254, 3060, 1681, 1635, 1604, 1549, 1470,
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1446, 1338, 852, 780, 691. H NMR (500 MHz, CDCl3) δ 8.25-8.22 (m, 2H),
7.82-7.81 (m, 2H), 7.61 (d, J = 16.0 Hz, 1H), 7.49-7.46 (m, 1H), 7.27-7.23 (m, 4H),
7.06-7.00 (m, 3H), 6.81 (d, J = 7.5 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ
161.1, 152.7, 147.2, 146.3, 134.8, 132.6, 129.5, 127.9, 127.0, 126.8, 123.0, 121.6 (d, J
= 6.1 Hz), 121.2, 117.5 (dd, J1 = 9.0 Hz, J2 = 24.6 Hz), 117.2 (dd, J1 = 8.8 Hz, J2 =
25.1 Hz), 114.6, 114.4 (dd, J1 = 2.9 Hz, J2 = 24.3 Hz). HRMS (ESI) calcd for
C22H16F2N3O1 [M+H]+: 376.1256, found 376.1250.
(E)-2-(2,4-Dichlorostyryl)-3-(phenylamino)quinazolin-4(3H)-one (1z): Pale-yellow
solid (85%). 1H NMR (500 MHz, CDCl3) δ 8.47 (d, J = 16.0 Hz, 1H), 8.23 (d, J = 8.0
Hz, 1H), 7.83 (m, 2H), 7.57-7.44 (m, 4H), 7.28-7.26 (m, 2H), 7.21 (m, 2H), 7.01 (t, J
= 7.5 Hz, 1H), 6.81 (d, J = 8.0 Hz, 2H); C{1H} NMR (125 MHz, CDCl3) δ 161.1,
13
152.6, 147.3, 146.3, 136.1, 135.7, 135.4, 134.8, 132.4, 129.9, 129.6, 128.4, 128.0,
127.5, 126.9, 126.8, 123.0, 121.2, 114.6. HRMS (ESI) calcd for C22H16Cl2N3O1
[M+H]+: 408.0665, found 408.0669.
(E)-3-(Isopropylamino)-2-styrylquinazolin-4(3H)-one (1za): Pale-yellow solid
(1.34 g, 88%). IR (KBr) v (cm-1): 3261, 2967, 1678, 1632, 1607, 1546, 1467, 1448,
1336, 873, 771, 689. 1H NMR (500 MHz, CDCl3) δ 8.26 (d, J = 8.0 Hz, 1H), 8.06 (d,
J = 16.0 Hz, 1H), 7.79 (m, 3H), 7.66 (d, J = 7.5 Hz, 2H), 7.46-7.37 (m, 4H), 5.60 (d, J
= 4.0 Hz, 1H), 3.42 (m, 1H), 1.15 (m, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ
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161.8, 153.1, 147.3, 140.0, 135.9, 134.4, 129.6, 128.9, 127.9, 127.4, 126.7, 126.1,
120.6, 119.4, 51.8, 20.8. HRMS (ESI) calcd for C19H20N3O1 [M+H]+: 306.1601,
found 306.1601.1,2-Diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2a): Yellow solid
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(53.3 mg, 79%), mp 256-257 C (lit.7a 257-258 C). H NMR (500 MHz, CDCl3) δ
8.23 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 4.0 Hz, 2H), 7.57-7.55 (m, 2H), 7.40-7.30 (m,
9H), 6.66 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.7, 156.5, 152.0, 149.5,
140.1, 133.9, 130.7, 129.6, 129.0, 128.9, 128.8, 128.0, 126.6, 126.2, 124.1, 118.0,
101.9. HRMS (ESI) calcd for C22H16N3O1 [M+H]+: 338.1288, found 338.1284.
8-Methyl-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2b): Yellow solid
o
(59.7 mg, 85%), mp 257-258 C. IR (KBr) v (cm-1): 3055, 2960, 1675, 1614, 1590,
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1557, 1491, 1472, 1449, 1360, 799, 763, 689. H NMR (500 MHz, DMSO-d6) δ
7.70-7.68 (m, 2H), 7.61 (t, J = 8.0 Hz, 1H), 7.51-7.41 (m, 6H), 7.34-7.29 (m, 3H),
7.11 (d, J = 7.0 Hz, 1H), 7.01 (s, 1H), 2.67 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 159.5, 157.3, 152.3, 151.5, 141.2, 140.7, 133.2, 130.7, 129.4, 129.2, 129.1, 128.9,
128.4, 127.7, 126.9, 124.8, 116.9, 102.2, 23.5. HRMS (ESI) calcd for C23H18N3O1
[M+H]+: 352.1445, found 352.1441
7-Methyl-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2c): Yellow solid,
(58.3 mg, 83%), mp 238-239 oC (lit.7a 238-239 oC). 1H NMR (500 MHz, DMSO-d6) δ
7.83 (s, 1H), 7.72-7.70 (m, 2H), 7.64-7.59 (m, 2H), 7.46-7.40 (m, 5H), 7.33-7.29 (m,
3H), 7.05 (s, 1H), 2.41 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.7, 156.6,
151.7, 147.8, 140.5, 135.8, 134.3, 130.7, 129.6, 129.1, 129.0, 128.9, 128.3, 128.1,
126.3, 125.8, 118.0, 102.2, 21.4. HRMS (ESI) calcd for C23H18N3O1 [M+H]+:
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352.1445, found 352.1440.
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6-Methyl-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2d): Yellow solid
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9
o
(56.2 mg, 80%), mp 257-258 C. IR (KBr) v (cm-1): 3064, 2956, 1681, 1618, 1588,
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1544, 1483, 1447, 1360, 777, 758, 691. 1H NMR (500 MHz, DMSO-d6) δ 7.93 (d, J =
8.5 Hz, 1H), 7.71-7.69 (m, 2H), 7.48-7.41 (m, 6H), 7.33-7.30 (m, 3H), 7.21 (d, J = 8.0
Hz, 1H), 7.06 (s, 1H), 2.47 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.8, 156.6,
152.3, 150.0, 144.9, 140.4, 130.7, 129.6, 129.1, 129.0, 128.9, 128.3, 128.2, 126.4,
126.2, 126.0, 115.8, 102.2, 22.2. HRMS (ESI) calcd for C23H18N3O1 [M+H]+:
352.1445, found 352.1442.
5,6-Dimethyl-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2e): Yellow solid
o
1
(59.9 mg, 82%), mp 195-196 C. H NMR (500 MHz, CDCl3) δ 8.01 (d, J = 8.0 Hz,
1H), 7.56-7.55 (m, 2H), 7.38-7.26 (m, 8H), 7.16 (d, J = 8.5 Hz, 1H), 6.72 (s, 1H),
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2.64 (s, 3H), 2.45 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 158.4, 156.8, 151.1,
148.1, 142.4, 140.4, 132.1, 130.5, 129.4, 128.9, 128.8, 128.7, 128.3, 128.0, 126.6,
123.3, 116.1, 102.6, 21.0, 13.5. HRMS (ESI) calcd for C24H20N3O1 [M+H]+:
366.1601, found 366.1603
7-Methoxy-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2f): Yellow solid
o
(63.9 mg, 87%), mp 199-200 C. IR (KBr) v (cm-1): 3051, 2992, 1671, 1622, 1590,
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1569, 1484, 1453, 1354, 760, 703, 626. H NMR (500 MHz, DMSO-d6) δ 7.72-7.71
(m, 2H), 7.65 (d, J = 8.5 Hz, 1H), 7.47-7.41 (m, 7H), 7.33-7.29 (m, 3H), 7.07 (s, 1H),
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3.82 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 158.2, 156.7, 156.4, 150.6, 144.7,
140.5, 130.7, 129.7, 129.1, 129.0, 128.9 128.3, 128.2, 128.1, 125.3, 118.7, 105.1,
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102.2, 55.8. HRMS (ESI) calcd for C23H18N3O2 [M+H]+: 368.1394, found 368.1394
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7-Fluoro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2g): Yellow solid
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9
o
(49.7 mg, 70%), mp 240-242 C. IR (KBr) v (cm-1): 3060, 1680, 1624, 1571, 1559,
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1478, 1456, 1345, 774, 761, 693. H NMR (500 MHz, DMSO-d6) δ 7.99 (d, J = 2.5
Hz, 1H), 7.82-7.80 (m, 1H), 7.72-7.69 (m, 3H), 7.49-7.48 (m, 2H), 7.42 (d, J = 7.0
Hz, 3H), 7.34-7.32 (m, 3H), 7.11 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.1,
158.6, 158.2, 155.7, 155.6, 151.5, 146.1, 139.9, 130.8, 129.7, 129.1, 129.0, 128.9,
128.8, 128.4 (d, J = 8.1 Hz), 128.1, 127.9, 126.4, 123.0 (d, J = 24.7 Hz), 118.7 (d, J =
8.5 Hz), 110.8 (d, J = 23.7 Hz), 101.6. HRMS (ESI) calcd for C22H15F1N3O1 [M+H]+:
356.1194, found 356.1192
6-Fluoro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2h): Yellow solid
(46.2 mg, 65%), mp 264-265 C. IR (KBr) v (cm-1): 3041, 1683, 1625, 1587, 1558,
o
1
1474, 1446, 1366, 772, 759, 690. H NMR (500 MHz, DMSO-d6) δ 8.12-8.09 (m,
1H), 7.71-7.69 (m, 2H), 7.49-7.47 (m, 2H), 7.43-7.41 (m, 4H), 7.34-7.32 (m, 3H),
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7.26-7.22 (m, 1H), 7.08 (s, 1H); C{1H} NMR (125 MHz, CDCl3) δ 167.5, 165.5,
159.0, 155.8, 152.7, 139.7, 130.9, 129.8, 129.3 (d, J = 11.1 Hz), 129.1, 129.0, 128.9,
128.8, 128.1, 127.8, 114.6, 113.3 (d, J = 24.3 Hz), 110.7 (d, J = 22.0 Hz), 101.33.
HRMS (ESI) calcd for C22H15F1N3O1 [M+H]+: 356.1194, found 356.1195
8-Chloro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2i): Yellow solid
(52.7 mg, 71%), mp 200-202 C. IR (KBr) v (cm-1): 3055, 1687, 1613, 1588, 1534,
o
1
1490, 1449, 1363, 801, 765, 691. H NMR (500 MHz, DMSO-d6) δ 8.04 (d, J = 8.5
Hz, 1H), 7.72-7.68 (m, 3H), 7.49-7.47 (m, 2H), 7.44-7.37 (m, 4H), 7.35-7.32 (m, 3H),
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7.10 (s, 1H); C{1H} NMR (125 MHz, CDCl3) δ 159.1, 156.1, 152.9, 150.7, 140.2,
139.9, 131.0, 129.9, 129.2, 129.1, 129.0, 128.3, 128.1, 128.0, 125.8, 124.8, 116.5,
101.8. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898, found 372.0894
7-Chloro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2j): Yellow solid
(52.0 mg, 70%), mp 235-236 oC (lit.7a 237-238 oC). 1H NMR (500 MHz, DMSO-d6) δ
7.99-7.98 (m, 1H), 7.82-7.79 (m, 1H), 7.72-7.69 (m, 3H), 7.49-7.42 (m, 5H),
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7.34-7.32 (m, 3H), 7.11 (s, 1H); C{1H} NMR (125 MHz, CDCl3) δ 159.0, 155.6,
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152.3, 148.3, 139.9, 134.5, 130.9, 129.9, 129.6, 129.2, 129.1, 129.0, 128.2, 128.1,
128.0, 125.8, 118.9, 101.9. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898,
found 372.0898
6-Chloro-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2k): Yellow solid
(51.2 mg, 69%), mp 246-247 oC (lit.7a 246-247 oC). 1H NMR (500 MHz, DMSO-d6) δ
8.04 (d, J = 8.5 Hz, 1H), 7.72-7.69 (m, 3H), 7.49-7.48 (m, 2H), 7.43-7.37 (m, 4H),
7.34-7.33 (m, 3H), 7.10 (s, 1H); C{1H} NMR (125 MHz, CDCl3) δ 159.1, 156.1,
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152.9, 150.7, 140.3, 139.9, 131.0, 129.9, 129.2, 129.1, 129.0, 128.3, 128.1, 128.0,
125.7, 124.8, 116.5, 101.8. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898,
found 372.0897
7-Bromo-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2l): Yellow solid
(64.8 mg, 78%), (lit.7a 259-260 oC), mp 260-261 C. 1H NMR (500 MHz, DMSO-d6)
o
δ 8.13-8.12 (m, 1H), 7.92-7.90 (m, 1H), 7.70-7.69 (m, 2H), 7.63 (d, J = 9.0 Hz, 1H),
7.49-7.42 (m, 5H), 7.34-7.32 (m, 3H), 7.10(s, 1H); 13C{1H} NMR (125 MHz, CDCl3)
δ 159.1, 155.5, 152.4, 148.6, 139.9, 137.2, 131.0, 129.9, 129.2, 129.1, 129.0, 128.9,
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128.3, 128.2, 128.0, 119.4, 117.1, 101.9. HRMS (ESI) calcd for C22H15Br1N3O1
[M+H]+: 416.0393, found 416.0397
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7-Iodo-1,2-diphenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2m): Yellow solid (65.8
mg, 71%), mp 250-252 oC. IR (KBr) v (cm-1): 3061, 1673, 1603, 1581, 1533, 1489,
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1460, 1333, 828, 764, 694. H NMR (500 MHz, DMSO-d6) δ 8.31-8.30 (m, 1H),
8.05-8.02 (m, 1H), 7.70-7.69 (m, 2H), 7.49-7.46 (m, 3H), 7.42 (d, J = 7.0 Hz, 3H),
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7.33-7.32 (m, 3H), 7.09 (s, 1H); C{1H} NMR (125 MHz, CDCl3) δ 159.2, 155.2,
152.5, 149.1, 142.6, 139.9, 135.5, 131.0, 129.9, 129.2, 129.1, 129.0, 128.4, 128.2,
128.0, 119.8, 101.9, 87.3. HRMS (ESI) calcd for C22H15I1N3O1 [M+H]+: 464.0255,
found 464.0258
1,2-Diphenyl-7-(trifluoromethyl)pyrazolo[5,1-b]quinazolin-9(1H)-one
(2n):
o
Yellow solid (48.6 mg, 60%), mp 248-250 C. IR (KBr) v (cm-1): 2959, 1684, 1590,
1548, 1533, 1488, 1453, 1316, 838, 767, 668. 1H NMR (500 MHz, CDCl3) δ 8.52 (s,
1H), 7.90-7.88 (m, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.56-7.54 (m, 2H), 7.40-7.33 (m,
8H), 6.69 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.1, 155.8, 153.1, 151.5,
139.3, 131.0, 129.9, 129.9, 129.1, 129.0, 128.9, 128.2, 127.5, 127.1, 126.4, 125.8,
125.5, 125.1, 124.8 (d, J = 4.3 Hz), 122.9, 117.1, 101.4. HRMS (ESI) calcd for
C23H14F3N3O1Na [M+Na]+: 428.0987, found 428.0972
2-Phenyl-1-(o-tolyl)pyrazolo[5,1-b]quinazolin-9(1H)-one (2o): Yellow solid (47.1
o
mg, 67%), mp 220-221 C. IR (KBr) v (cm-1): 3081, 1684, 1601, 1548, 1560, 1479,
1
1456, 1345, 815, 767, 698. H NMR (500 MHz, DMSO-d6) δ 8.05 (d, J = 7.0 Hz,
1H), 7.80-7.77 (m, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.59-7.58 (m, 2H), 7.43-7.41 (m,
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3H), 7.36 (t, J = 8.0 Hz, 1H), 7.26-7.24 (m, 3H), 7.15-7.12 (m, 1H), 7.04 (s, 1H), 2.29
(s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 157.1, 156.4, 151.5, 149.9, 138.4, 137.9,
134.0, 131.1, 130.7, 130.1, 128.9, 128.8, 128.6, 128.2, 126.7, 126.6, 126.3, 123.8,
117.7, 100.5, 18.2. HRMS (ESI) calcd for C23H18N3O1 [M+H]+: 352.1445, found
352.1447
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2-Phenyl-1-(m-tolyl)pyrazolo[5,1-b]quinazolin-9(1H)-one (2p): Yellow solid (57.6
o
mg, 82%), mp 241-242 C. IR (KBr) v (cm-1): 3076, 1682, 1592, 1550, 1488, 1467,
1
1447, 1362, 808, 770, 688. H NMR (500 MHz, DMSO-d6) δ 8.05 (d, J = 8.0 Hz,
1H), 7.81-7.68 (m, 4H), 7.43-7.32 (m, 5H), 7.23-7.20 (m, 2H), 7.11 (d, J = 7.5 Hz,
1H), 7.07 (s, 1H), 2.21 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.0, 156.6,
152.2, 149.8, 140.2, 139.0, 134.0, 130.8, 130.5, 129.1, 128.9, 128.7, 128.2, 128.1,
126.7, 126.4, 125.3, 124.2, 118.1, 102.0, 21.4. HRMS (ESI) calcd for C23H18N3O1
[M+H]+: 352.1445, found 352.1439
2-Phenyl-1-(p-tolyl)pyrazolo[5,1-b]quinazolin-9(1H)-one (2q): Yellow solid (56.2
mg, 80%), mp 273-274 oC (lit.7a 273-274 oC). 1H NMR (500 MHz, DMSO-d6) δ 8.05
(d, J = 7.0 Hz, 1H), 7.81-7.78 (m, 1H), 7.72-7.67 (m, 3H), 7.43-7.33 (m, 6H), 7.12 (d,
J = 8.0 Hz, 2H), 7.06 (s, 1H), 2.24 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.7,
156.4, 151.8, 149.2, 139.8, 137.3, 134.0, 130.7, 129.6, 129.1, 128.8, 128.0, 127.9,
126.6, 126.0, 124.1, 117.8, 101.4, 21.3. HRMS (ESI) calcd for C23H18N3O1 [M+H]+:
352.1445, found 352.1444
1-(4-Methoxyphenyl)-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2r): Yellow
o
solid (62.4 mg, 85%), mp 244-245 C. IR (KBr) v (cm-1): 3080, 1676, 1597, 1553,
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1507, 1463, 1449, 1328, 844, 760, 686. 1H NMR (500 MHz, CDCl3) δ 8.23 (d, J = 8.0
Hz, 1H), 7.74-7.73 (m, 2H), 7.57-7.55 (m, 2H), 7.38-7.31 (m, 6H), 6.80 (d, J = 9.0
Hz, 2H), 6.67 (s, 1H), 3.75 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 160.1, 158.6,
156.5, 151.8, 149.2, 134.0, 132.2, 130.7, 129.6, 129.0, 128.8, 128.0, 126.6, 125.9,
124.1, 117.9, 114.0, 101.2, 55.4. HRMS (ESI) calcd for C23H18N3O2 [M+H]+:
368.1394, found 368.1405
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1-(2-Chlorophenyl)-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2s): Yellow
o
solid (40.8 mg, 55%), mp 215-216 C. IR (KBr) v (cm-1): 3060, 1680, 1587, 1548,
1489, 1467, 1448, 1325, 811, 766, 689. 1H NMR (500 MHz, DMSO-d6) δ 8.06 (d, J =
8.0 Hz, 1H), 7.84-7.78 (m, 2H), 7.69-7.66 (m, 3H), 7.46-7.36 (m, 7H), 7.06 (s, 1H);
13C{1H} NMR (125 MHz, CDCl3) δ 157.0, 156.4, 151.4, 149.8, 136.4, 134.8, 134.1,
131.7, 131.3, 130.9, 130.4, 129.0, 128.9, 127.8, 127.3, 126.6, 126.5, 124.0, 117.7,
101.3. HRMS (ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898, found 372.0889
1-(3-Chlorophenyl)-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2t): Yellow
o
solid (52.0 mg, 70%), mp 208-209 C. IR (KBr) v (cm-1): 3056, 1674, 1597, 1550,
1489, 1467, 1447, 1328, 792, 762, 694. 1H NMR (500 MHz, DMSO-d6) δ 8.07 (d, J =
7.0 Hz, 1H), 7.83-7.79 (m, 1H), 7.74-7.69 (m, 4H), 7.46-7.32 (m, 7H), 7.10 (s, 1H);
13C{1H} NMR (125 MHz, CDCl3) δ 158.9, 156.6, 152.1, 149.7, 141.5, 134.6, 134.2,
131.1, 130.1, 129.9, 129.1, 129.0, 128.0, 127.8, 126.6, 124.6, 118.2, 102.9. HRMS
(ESI) calcd for C22H15Cl1N3O1 [M+H]+: 372.0898, found 372.0894
1-(4-Chlorophenyl)-2-phenylpyrazolo[5,1-b]quinazolin-9(1H)-one (2u): Yellow
o
o
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solid (49.0 mg, 66%), mp 220-221 C (lit.7a 220-221 C). H NMR (500 MHz,
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